Temperature Correction of Blood Gas Measurements during Therapeutic Hypothermia: Is it Time to Chill Out? Dr. Elizabeth Zorn Dr. Gwenyth Fischer Dr. Martha Lyon
Disclosures (ML) • Speaking Honoraria – Radiometer – Nova Biomedical – Draeger • Research Support (Reagents, Instrumentation, Travel) – Nova Biomedical – Roche Diagnostics (Canada) – Radiometer – Instrumentation Laboratories (Canada) • ALOL Biomedical Inc • Clinical Laboratory Consulting Business
Disclosures (EZ) • Nothing to disclose
Disclosures (GF) • Nothing to disclose
Objectives 1) To describe the pathophysiology of newborn hypoxic ischemic encephalopathy (HIE) 2) To discuss why therapeutic hypothermia is an effective treatment for HIE. 3) To review the alpha-stat versus the pH- stat strategies (and limitations of each) for measuring and reporting blood gas results during therapeutic hypothermia. 4) To outline the inconsistency in the measurement and reporting of blood gas parameters in the published clinical trials that demonstrated the efficacy of therapeutic hypothermia 5) To present clinical cases and discuss how the inconsistency in reporting blood gas results could influence the care of the neonate.
Clinical Case Example • An outside hospital calls to request transport for a newborn • 39w5d gestation female infant, birth weight 3050 g • Mother presented to hospital with spontaneous rupture of membranes, meconium-stained fluid • During fetal monitoring, noted to have “down tones” so stat C section was performed
Clinical Case Example • At delivery, infant is limp, blue, and pulseless • Immediately intubated, received chest compressions, epinephrine, bicarb, and calcium • Required chest compressions for 20 minutes, multiple doses of epinephrine • APGARs were 0, 1, 1, 1, 1 at 1, 5, 10, 15, and 20 minutes of age • Arterial blood gas: pH 6.75, CO2 123, O2 108, HCO3 17
Clinical Case Example • When our transport team arrived, infant was noted to be intubated and unresponsive • Passive cooling initiated during transport to our facility • Upon arrival, examination showed an unresponsive infant with no purposeful movements, minimal pupillary reaction to light, and intermittent lip-smacking and upper extremity jerking • Admission temperature 32.7⁰C • Seizure activity confirmed on a EEG
Clinical Case Example • Admission laboratory data: • Na 143, K 3.6, Cl 102, CO2 12, BUN 8, Creatinine 0.78, Glucose 165 • ALT 142, AST 312 • Lactate 19 • ABG 7.11/38/87/12/-16 • WBC 35.9, hgb 14.6, plt 142 • INR 2.4, PTT 88, fibrinogen 98
Clinical Case Example • Plan: • Neuro: Initiate therapeutic hypothermia (33.5°C for 72 hours). Loaded with phenobarbital x2 and keppra for seizures. • FEN: TPN with total fluids written for 40 ml/kg/day due to anuria. • Respiratory: Conventional mechanical ventilation • CV: Dopamine and hydrocortisone started for hypotension • ID: Started on ampicillin, gentamycin, and acyclovir (mother with HSV but treated during pregnancy and infant delivered via c-section) • Heme: Coagulopathy treated with FFP and cryoprecipitate, continue to monitor coags • Sedation: Fentanyl prn
Neonate – Hypoxic Ischemic Encephalopathy (HIE) • Lack of oxygen in the brain around the time of birth (perinatal asphyxia) affects 3-5 infants/1000 live births • 0.5-1 infants per 1000 live births develop brain damage in the form of HIE • Up to 60% of infants with HIE will die and 25% of survivors will have long term neurodevelopmental sequelae
• Therapeutic mild hypothermia (33.5⁰C) is currently the only neuroprotective treatment to have been clinically tested in large trials to minimize brain injury in term newborns • Prior to the hypothermia clinical trials, supportive measures (no specific therapies) were only available for HIE
Which babies are eligible for therapeutic hypothermia? • Therapeutic mild hypothermia (33.5⁰C) is currently the only neuroprotective treatment to have been clinically tested in large trials to minimize brain injury in term newborns • Prior to the hypothermia clinical trials, supportive measures (no specific therapies) were only available for HIE
Which babies are eligible for therapeutic hypothermia? • Therapeutic mild hypothermia (33.5⁰C) is • Based on inclusion criteria published in clinical trials currently the only neuroprotective treatment to have been clinically tested in large trials to minimize brain injury in term newborns • Prior to the hypothermia clinical trials, supportive measures (no specific therapies) were only available for HIE
Which babies are eligible for therapeutic hypothermia? • Therapeutic mild hypothermia (33.5⁰C) is • Based on inclusion criteria published in clinical trials currently the only neuroprotective • ≥ 36 weeks gestation and ≤6 hours of age treatment to have been clinically tested in large trials to minimize brain injury in term newborns • Prior to the hypothermia clinical trials, supportive measures (no specific therapies) were only available for HIE
Which babies are eligible for therapeutic hypothermia? • Therapeutic mild hypothermia (33.5⁰C) is • Based on inclusion criteria published in clinical trials currently the only neuroprotective • ≥ 36 weeks gestation and ≤6 hours of age treatment to have been clinically tested in large • pH ≤ 7.0 or a base deficit of ≥ 16 mmol/L (cord blood or blood trials to minimize brain collected within the first hour of birth) injury in term newborns • Prior to the hypothermia clinical trials, supportive measures (no specific therapies) were only available for HIE
Which babies are eligible for therapeutic hypothermia? • Therapeutic mild hypothermia (33.5⁰C) is • Based on inclusion criteria published in clinical trials currently the only neuroprotective • ≥ 36 weeks gestation and ≤6 hours of age treatment to have been clinically tested in large • pH ≤ 7.0 or a base deficit of ≥ 16 mmol/L (cord blood or blood trials to minimize brain collected within the first hour of birth) injury in term newborns • History of an acute perinatal event • Prior to the hypothermia clinical trials, supportive measures (no specific therapies) were only available for HIE
Which babies are eligible for therapeutic hypothermia? • Therapeutic mild hypothermia (33.5⁰C) is • Based on inclusion criteria published in clinical trials currently the only neuroprotective • ≥ 36 weeks gestation and ≤6 hours of age treatment to have been clinically tested in large • pH ≤ 7.0 or a base deficit of ≥ 16 mmol/L (cord blood or blood trials to minimize brain collected within the first hour of birth) injury in term newborns • History of an acute perinatal event • 10 minute APGAR score < 5 • Prior to the hypothermia clinical trials, supportive measures (no specific therapies) were only available for HIE
Which babies are eligible for therapeutic hypothermia? • Therapeutic mild hypothermia (33.5⁰C) is • Based on inclusion criteria published in clinical trials currently the only neuroprotective • ≥ 36 weeks gestation and ≤6 hours of age treatment to have been clinically tested in large • pH ≤ 7.0 or a base deficit of ≥ 16 mmol/L (cord blood or blood trials to minimize brain collected within the first hour of birth) injury in term newborns • History of an acute perinatal event • 10 minute APGAR score < 5 • Prior to the hypothermia • Assisted ventilation initiated at birth and continued for at clinical trials, supportive least 10 minutes measures (no specific therapies) were only available for HIE
Which babies are eligible for therapeutic hypothermia? • Therapeutic mild hypothermia (33.5⁰C) is • Based on inclusion criteria published in clinical trials currently the only neuroprotective • ≥ 36 weeks gestation and ≤6 hours of age treatment to have been clinically tested in large • pH ≤ 7.0 or a base deficit of ≥ 16 mmol/L (cord blood or blood trials to minimize brain collected within the first hour of birth) injury in term newborns • History of an acute perinatal event • 10 minute APGAR score < 5 • Prior to the hypothermia • Assisted ventilation initiated at birth and continued for at clinical trials, supportive least 10 minutes measures (no specific • Neurologic examination demonstrating moderate to severe therapies) were only available for HIE encephalopathy is essential
Pathophysiology of HIE
Pathophysiology of HIE
How/Why is Hypothermia Neuroprotective? • Reducing brain perfusion and metabolism
How/Why is Hypothermia Neuroprotective? • Reducing brain perfusion and metabolism • Decrease of cellular oxygen and glucose requirements by 5- 8% per ⁰C decrease in temperature • This leads to a decrease in CO 2 production • Hypocapnia with normoxemia induces cerebral vasoconstriction and decreases cerebral blood flow • Mitigate reperfusion injury
How/Why is Hypothermia Neuroprotective? • Reducing brain perfusion and metabolism • Decrease free radical production
How/Why is Hypothermia Neuroprotective? • Reducing brain perfusion and metabolism • Decrease free radical production • Decrease the immune response
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